Molecular mechanisms coordinating between cell cycle and differentiation in lung epithelial cells

cyclin D1的转录功能，其失调在人类癌症中经常被观察到，已被认为有助于癌症的形成。我们发现cyclin D1蛋白通过直接与RUNX3结合抑制RUNX3活性，b干扰其与肺癌细胞中p300的相互作用。Cyclin D1抑制p300依赖性RUNX3乙酰化，负调控Cyclin依赖性激酶（cdk）抑制剂p21的表达。细胞周期蛋白D1的这些转录作用不需要cdk4/6激酶激活。我们提出cyclin D1提供了一个转录开关，允许RUNX3的肿瘤抑制活性在癌细胞中被抑制。

Transcriptional function of cyclin D1, whose deregulation is frequently observed in human cancers, has been suggested to contribute to cancer formation. We show that cyclin D1 protein inhibits RUNX3 activity by directly binding to it andB interfering with its interaction with p300 interaction in lung cancer cells. Cyclin D1 inhibits p300-dependent RUNX3 acetylation and negatively regulates cyclin-dependent kinase (cdk) inhibitor p21 expression. These transcriptional effects of cyclin D1 do not require cdk4/6 kinase activation. We propose that cyclin D1 provides a transcriptional switch that allows the tumor suppressor activity of RUNX3 to be repressed in cancer cells.